Prospective Validation of Circulating Tumor Cells & Circulating Endothelial Cells as Biomarkers in Renal Cancer

NCT02499458 | Completed DMC

• 1 other identifier: 105484
• Study Type: observational
• Target: 44
• Locations: 1 country
• Sites: 1

Brief Summary

Circulating tumor cells (CTCs) have prognostic value in several tumor types, and increasing evidence suggests that molecular characterization of CTCs can serve as a "liquid biopsy" to understand and address treatment resistance. The goal of this proposal is to demonstrate that CTCs can be accurately enumerated and characterized in metastatic clear cell renal cancer (CCRC) and can serve as prognostic/predictive biomarkers to improve treatment. The challenge surrounding CTC analysis in CCRC is that most CTC technologies (including the clinical gold-standard CellSearch®) depend in epithelial markers such as EpCAM that are expressed at low or heterogeneous levels in CCRC. Members of the research team have developed a novel CTC microfluidic technology that can effectively detect CTCs that are completely undetectable by CellSearch® because of very low EpCAM expression, as well as allowing for CTC recovery for downstream molecular characterization. The goal of this proposal is therefore to test the hypotheses that (1) The microfluidics CTC technology will have better sensitivity/specificity relative to the CellSearch in metastatic CCRC; and (2) Enumeration of CTCs in metastatic CCRC patients (n=66) will have prognostic value, while molecular characterization of CTCs for expression of biomarkers (VHL, VEGF, mTOR, HIF1/HIF2, AKT) related to CCRC etiology will be predictive of response/resistance to targeted therapies. Although CCRC is relatively uncommon, the lack of established adjuvant treatments and high cost of targeted therapies in the palliative setting makes the search for new prognostic/predictive biomarkers an important clinical goal.

Conditions

Clear Cell Renal Cancer; Circulating Tumor Cells; Circulating Endothelial Cells; Prognostic Biomarkers; Predictive Biomarkers

Outcome Measures

Primary Outcomes (2)

• Sensitivity/specificity of CTC enumeration (microfluidics vs CellSearch)

  For comparison of the 2 CTC platforms, a Bland-Altman plot will be constructed. This plot is superior to standard correlation statistics in that it assesses agreement rather than association. Initially we will use a Chi-Square test to compare the 2 methods at a cutoff point of ≥5 versus \<5 CTCs/7.5mL, with simple comparison of PFS at this level. As the cut-off point may not be the same for each method, we will also compare the methods using simple 2X2 contingency tables.

  24 months

• Progression free survival (PFS).

  Survival analysis will be performed by Kaplan Meier and significance analysis will use the log-rank test. Cox multivariate analysis will be performed to look at the number and molecular characteristics of CTCs as independent prognostic parameters of survival.

  24 months

Secondary Outcomes (4)

• Overall survival (OS)

  24 months

• Radiological response

  within 16 weeks after start of study

• Molecular characterization of CTCs

  baseline, 4-6 weeks after start of therapy, 10-12 weeks after start of therapy, post-progression (up to 24 months)

• Enumeration of CECs

  baseline, 4-6 weeks after start of therapy, 10-12 weeks after start of therapy, post-progression (up to 24 months)

Interventions

None- observational study OTHER

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Oncology care centre

You may qualify if:

• ECOG performance status 0-2
• Age over 18 years
• Diagnosed renal cancer with clear cell histology
• Metastatic disease
• Predicted life expectancy over 2 months
• Targeted treatment with an anti-VEGF or anti-mTOR agent as first or second line therapy
• Planned for standard imaging within 16 weeks after start of therapy

You may not qualify if:

• Presence of substantial comorbidities (uncontrolled heart or respiratory dysfunction, severe renal or hepatic impairment \[Cl Cr below 30ml/h OR Bb\>3X ULN\])
• History of a malignancy other than non-melanoma skin cancer in the previous 5 years
• Any other contraindication to targeted treatments.

Sponsors & Collaborators

• London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's: lead
• London Health Sciences Centre: collaborator
• Hamilton Health Sciences Corporation: collaborator

Study Sites (1)

London Health Sciences Centre

London, Ontario, N6K 4L6, Canada

Location

MeSH Terms

Conditions

Neoplastic Cells, Circulating

Condition Hierarchy (Ancestors)

Neoplasm Metastasis; Neoplastic Processes; Neoplasms; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Alison L Allan, PhD

  London Health Sciences Centre

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: July 10, 2015
• First Posted: July 16, 2015
• Study Start: November 1, 2014
• Primary Completion: December 1, 2018
• Study Completion: December 1, 2018
• Last Updated: December 24, 2019

Record last verified: 2019-12

Locations

CA (1)